Luo Han Guo (also known as Luo Han Kuo) is a fruit of the Siraitia grosvenori Swingle (formerly Momoridca grosvenori Swingle) belonging to the Cucurbitaceae species. These fruits are cultivated in parts of China and extract of the Luo Han Guo plant is currently manufactured and marketed as a natural low-calorie sweetener, for example, PURELO™. U.S. Pat. No. 5,411,755 describes a process for preparing a sweet juice from Luo Han Guo fruit. The sweetness of the extract from Luo Han Guo is due to the presence of highly stable triterpene glycosides, known as mogrosides, which are about 250 to 300 times sweeter than sucrose. These compounds possess a triterpene backbone with two to six glucose units attached. Examples of cucurbitane glycosides purified from Siraitia grosvenori include 20-hydroxy-11-oxomogroside IA1, 11-oxomogroside IIE, 11-oxomogroside IA1, mogroside IIE, mogroside III, mogroside IV, mogroside V, siamenoside I, triterpenoid glycoside V, neogroside, Kaempferol 7-α-ι-rhamnopyranoside, Kaempferol 3,7-α-ι-dirhamnopyranoside, 11-oxomogroside III, 11-Dehydroxymogroside III, 11-oxomogroside IV, mogroside II, mogroside VI, 11-oxo-mogroside and siamcroside-I. Mogrosides have been shown to have beneficial effects in the treatment of diabetes, cancer and inflammation.
Statins are compounds that are known to have a lowering effect on levels of LDL-cholesterol in the human blood. Statins inhibit hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase, the rate-determining enzymatic step in cholesterol biosynthesis. Currently available statins include lovastatin, simvastatin, pravastatin, fluvastatin (LESCOL®, CANEF®), cerivastatin and atorvastatin. Fluvastatin (disclosed in U.S. Pat. No. 4,739,073) is administered as a sodium salt and is an entirely synthetic compound that is in part structurally distinct from the fungal derivatives of this class, which contain a hexahydronaphthalene ring.
Hepatitis C (HCV), formerly referred to as blood-borne non-A, non-B hepatitis virus (NANBV), is a transmissible disease which was first identified in individuals who had received blood transfusions. Chronic hepatitis C virus is an insidious and slow-progressing disease having a significant negative impact on the quality of life. It can eventually result in cirrhosis of the liver, decompensated liver disease and/or hepatocellular carcinoma.
Alpha interferon mono-therapy is commonly used to treat infection with chronic hepatitis C. However, this treatment is not always effective and sometimes results in intolerable side effects depending on the dosage and the duration of therapy.
The general anti-viral therapeutic Ribavirin has been proposed as a mono-therapy treatment for chronic hepatitis C infection. However, this mono-therapy treatment has been found to be relatively ineffective and, furthermore, presents its own undesirable side effects.
An alternative therapeutic approach combining alpha interferon and Ribavirin has also been proposed. Preliminary results suggest that such a combination therapy may be more effective then either alpha interferon or Ribavirin mono-therapy. However, the combined use of alpha interferon and Ribavirin does not eradicate HCV-RNA in a long-term, effective manner.
There is therefore a need to provide a therapy which has efficacy in the treatment of chronic hepatitis C infection. Desirably, such a therapeutic composition or treatment regimen will eradicate HCV-RNA in a long-term, effective manner.
Furthermore, in addition to the treatment of subjects infected with HCV, there is a pressing need to provide means of treating HCV-contaminated blood or blood products. Post-transfusion hepatitis (PTH) occurs in approximately 10% of transfused patients, with HCV accounting for up to 90% of these cases. The disease frequently progresses to chronic liver damage in 25 to 55% of cases.
Acquired immune deficiency syndrome (AIDS) is a disease characterized by failure of the immune system. It is attributable to a virus called human immunodeficiency virus (HIV), which is a member of the retrovirus family of lipid envelope viruses, which is very prevalent in the animal kingdom. HIV infects and takes over certain cells of the immune system, using these cells to replicate. This causes the infected cells to function improperly and die prematurely, thus weakening the immune system. HIV infection results in disturbances of the entire immune defense mechanism. In particular, T4 or helper cells are prevented from carrying out their role in the regulation of the immune response. This HIV-induced T4 reduction results in the development of frequent and eventually fatal opportunistic infections caused by pathogenic organisms such as viruses, bacteria, protozoa or fungi.
Anti-viral agents that inhibit replication of viruses have been known since the mid 1980's. The overall goal of anti-HIV therapy is to slow or stop the replication process, and thereby slow or stop the progression of HIV disease and the destruction of the immune system. Many drugs are now available for inhibiting the replication of the HIV virus. However, their side effects are often so severe that treatment must be halted allowing HIV resistant strains to quickly develop. Current anti-HIV therapies can be categorized into groups based on which step in the virus's life cycle they target or how they do it. Examples of anti-HIV therapies include nucleoside analogue reverse-transcriptase inhibitors, non-nucleoside analogue reverse-transcriptase inhibitors and protease inhibitors. The first two groups work by mimicking one of the building blocks of DNA and thus interfering with reverse transcription, a process essential for HIV replication. The third group, protease inhibitors, works at a later stage in the viral life cycle after the virus has successfully infected the cell and is attempting to replicate. These drugs ultimately slow down the replication of viral DNA. However, they do not rid the body of the virus but merely act to slow down and reduce the severity of the development of the infection.
The number of patients infected with HIV has significantly increased in recent years. There is therefore a need for the development of a more efficacious and less toxic treatment for HIV.
Many of the anti-viral therapies which are currently available are directed towards targeting viral components and are therefore prone to compensatory viral evasion mechanisms. Treatments aimed at interfering with, or preventing, viral replication, either by enhancing antiviral responses or by inhibiting proviral activities within the host cell have greater potential for controlling the virus without selective pressure on the virus itself to mutate in a compensatory manner.